Separation media prepared by packing particles in a cylindrical pipe or the like have been long widely used as an HPLC column, a cartridge for solid phase, a column for column chromatography, a column for pretreatment, a GC column and the like in chromatography.
Monolithic bodies have been invented as an alternative to such particles and have attracted attention. Monolithic bodies have a three-dimensional network skeleton and advantages thereof include higher porosity and higher separation ability at low pressures than those of particles.
However, these monolithic bodies alone are easily damaged and cannot be directly used as a separation medium. Therefore, an HPLC column is produced by covering it with a cylindrical plastic pipe, or a cartridge for solid phase is produced by fixing a monolithic body on a resin chip or cartridge.
Also, capillary monolithic columns for HPLC, which are produced by forming a monolithic body within a fused quartz tube having an inner diameter of 1 mm or less, are marketed.
At present, however, these methods fail to make full use of the advantages of monolithic bodies. In the case of commercially available Chromolith (registered trademark), a cylindrical monolithic body is prepared and the surface is mechanically polished, chemically treated and clad with a PEEK pipe to produce an HPLC column.
This method is disclosed in National Publication of International Application No. 2007-292751, and focuses on the poor separation efficiency of silica monolith having a small diameter, and as a result of the studies of the cause, an uneven structure of a silica gel layer has been found on the periphery of the silica monolith. As a measure for the improvement, it is suggested to reduce the diameter by grinding the outer peripheral layer when preparing a cylindrical monolithic body.
The method is employed for forming a monolithic column using a so-called clad which coats the resulting cylindrical monolithic body, the term meaning a sealed porous monolithic molded product designed so that liquid is allowed to flow from only one end of the cylinder, not from the side. Although it is necessary to form a most stable skeleton structure to prepare a cylindrical monolithic body having a high separation ability, making the side of the cylinder perfectly curved is difficult, and part of the ideal skeleton structure is broken by mechanical processing on the side. Therefore, the method is incapable of making full use of the ability of monolithic bodies.
Even if coating with resin is successfully done without mechanical processing, such resin is mainly composed of an organic polymer and has different properties from monolithic bodies mainly composed of inorganic silica gel. With PEEK resin, for example, hydrophobic adsorption occurs.
Also, although an inorganic binder is contained so as to improve the pressure resistance, the resin and the inorganic binder cause a specific separation behavior other than that of monolithic bodies.
Further, to coat with resin, it is necessary to raise the temperature up to a point higher than the softening point of the resin, and cladding leads to degradation of a chemically treated portion, failing to demonstrate high performance.
Also, as disclosed in International Publication Nos. 99/38006 and 99/50654, there is a technique of preparing a monolith in a fused quartz capillary. In this technique, the main components are the same, and so no specific separation behavior as in resin clad is found. However, it is considered that when forming a monolith in fused quartz, the inner diameter can only be at most about 1 mm, and about 0.2 mm to achieve high performance.
In this technique, the inner surface of fused silica and sol liquid are bonded and gelled to form a monolithic body. Upon gelation, however, the volume is reduced and the portion near the inner surface of the capillary is pulled by the bonding force with the inner surface, making it difficult to form a homogeneous skeleton. In a terrible case, the monolithic body is separated from the inner surface. Due to the bonding to the inner surface, the original, stable monolithic skeleton cannot be maintained, and the resulting monolithic body has poorer properties than those synthesized using a monolithic body alone.
Japanese Patent Laid-Open No. 2007-516821 proposes a chromatography column and a capillary prepared by etching the surface of a gel mold such as glass, glass-coated stainless steel or fused quartz to increase the surface area and chemical modification, and filling the gel mold with a monomer raw material to form pores by polymerization and aging.
In this method, the inner surface of the gel mold is etched or the inner surface area is increased by forming a coat by pre-treating with solution or slurry to strengthen the contact with monomers to be packed, and so achieving close contact is impossible.
An object of this method is to reduce voids formed between the gel mold and a monolithic molded article due to the shrinking process of the monolithic molded article as much as possible so as not to decrease the efficiency of separation in chromatography.
Further, to achieve the object, it is recommended to add particles of, for example, plastic, ceramic, glass or inorganic oxide of Ti, Al or Zr to reduce shrinkage of monolithic molded articles.
In addition, the publication also describes a method of using glass as the gel mold. However, even this method requires a step of etching the inner surface of the glass mold. Therefore, for strengthening the contact between the monomer and the mold as described above, it is not possible to achieve close contact between the two or to integrate them, and so the void formed between them still affects the separation ability.